The goal of the program described here is to develop an antiviral drug for treating and preventing Lassa fever and other hemorrhagic fevers of arenavirus origin. Previous library screening identified several good candidate small molecule inhibitors of Lassa virus entry. Subsequent in vitro and in vivo characterization identified a potent series, ST-193, with broad- spectrum activity against 5 distinct Category A hemorrhagic fever Arenaviruses. This series has shown protective efficacy in two animal models of Lassa fever, guinea pigs and cynomolgus monkeys. The specific objective of this application is to optimize this chemical series to identify an appropriate candidate for preclinical development and to collect the necessary data to support the submission of an application for an Investigational New Drug (IND).